Selective Bilateral Vestibular Neuropathy in a Turkish CMT1B Family With a Novel MPZ Mutation

Abstract

Purpose of review: To report the findings in 12 members over 3 generations of a family with dominantly inherited Charcot-Marie-Tooth disease (CMT1B) due to a novel MPZ mutation, who all had moderately severe selective impairment of vestibular function with normal hearing. Methods used were video head impulse testing of the function of all 6 semicircular canals, Romberg test on foam, nerve conduction studies, and whole exome and Sanger sequencing.

Recent findings: All affected patients had a demyelinating neuropathy and a novel MPZ mutation: c.362A>G (chr1: 161276584, p.D121G). All also had normal hearing for age but a moderately severe impairment of semicircular canal function and a positive Romberg test on foam.

Summary: Some CMT mutations can impair vestibular function, presumably because of a vestibular nerve involvement but spare hearing. In such patients, impairment of vestibular function and impairment of proprioception contribute to imbalance.

Figure 1. Family Tree

Each clinically affected patient is also electrophysiologically affected (indicated by dotted symbols) and is MPZ mutation positive (indicated by crimson shading and a plus sign “+”). Conversely, each MPZ mutation-positive patient is clinically and electrophysiologically affected. Patient IV.4 (unaffected) has 5 unaffected children; only the youngest (age 4) is indicated with a symbol; the ages of the other 4 are appended. The only exception is patient V.13, a clinically affected, MPZ-positive 3 years old, too young to cooperate with electrophysiologic or vestibular testing. The arrow indicates index case.

Figure 2. Video Head Impulse Testing

A typical example, from patient III.6, a woman aged 55. Vestibulo-ocular reflex (VOR) gain is reduced from each of the 6 semicircular canals (SCCs). Head velocity is shown in blue for 30 leftward head impulses and in orange for 30 rightward head impulses in the plane of each SCC. VOR eye velocity is shown in green. Catch-up saccades compensating for any VOR inadequacy are shown in red. This patient happens to make fewer catch-up saccades in response to head impulses in the right anterior-left posterior canal plane. In the centre of the figure, VOR gains are illustrated as a polar plot.